New concepts in gas chromatographic technology are proposed which will permit rapid and sensitive (10 to the minus 12th power g) quantitation of drugs in biological fluids. The principal objectives are to: (1) investigate methods for preparing high resolution organo-silicate coated open tubular glass capillaries, (2) perfect a dual gas chromatograph previously fabricated in the Principal Investigator's laboratory for analysis of drugs in extracts from biological fluids (no other prior clean-up), (3) evaluate the performance of the combined technology utilizing clonidine, guanethidine, hydralazine and norethindrone as test drugs and developing assay procedures for these drugs, and (4) conduct a pharmacokinetic and steady state study on clonidine in rabbit plasma in order to demonstrate the practicality of the dual gas chromatograph equipped with glass capillaries and electron capture detection. Twenty-six organo-silicates will be prepared of the Si-O-Si and Si-C chemical type which will possess a mono-layer of functional groups similar or identical to those in non-polar (SE-30, OV-101, UCW-98) semi-polar (OV-17, OV-225, OV-210, QF-1) and polar (poly I-110, poly A-103) gas chromatographic stationary phases. The dispersion and spreading deficiency of organo-silicate/stationary phase combinations in glass capillaries will be examined and the utility of capillary columns will be tested with drugs and in particular with clonidine, guanethidine, hydralazine and norethindrone isolated from plasma of orally dosed rabbits. Micro-packed capillary traps for isolating "chromatographic windows" in the first oven of the dual gas chromatograph will be prepared and tested for efficiency of transfer to the second oven. A valving sample-trapping network will be perfected which will permit multiple fractionation of a sample for the parent drug and its metabolites. Clonidine in rabbit plasma from single (pharmacokinetic) and multiple (steady state study) oral doses will be extracted, derivatized and assayed directly by the dual gas chromatograph and compared to radiochemical techniques.